Project Summary/Abstract Regenerative therapies using stem cells are being explored for treatment of advanced lung diseases such as emphysema. We recently identified an undifferentiated ?fibroblast-like? multipotent stromal cell (LMSC) from lung tissue that expresses the same surface markers (CD44, CD73, CD90, CD105) as multipotent bone marrow stromal cells and displays regenerative capacity following transplantation in mice and sheep with experimental emphysema. LMSCs from adult human lung tissue have elastogenic capacity in vitro, spontaneously form alveolar-like structures in matrigel. and secrete growth factors including FGF2, FGF7, FGF10, and HGF that can promote remodeling. In collaboration with the Production Assistance for Cellular Therapies (PACT) group at the Dana Farber Cancer Institute, we have developed procedures for manufacturing clinical grade LMSCs from biopsy specimens, and designed a biopolymer scaffold to promote lung engraftment of LMSCs following endobronchial administration. These technological advances make autologous LMSC transplantation feasible for human applications, addressing problems of rejection and the need for immunosuppression that are associated with allogeneic transplantation. The objectives of this project are: 1) to complete the preclinical pharmacotoxicology testing required to begin human trials; and 2) initiate Phase 1 trials of autologous LMSC transplantation in emphysema patients awaiting lung transplantation. This trial design will allow us to recover the LMSC-treated organ for histological analysis to characterize responses to LMSC treatment at the cellular level.